Background: Preoperative serum CA19-9 and histology grade could reflect the biological characteristics of pancreatic ductal adenocarcinoma (PDAC). This study aims to explore the combined effect of preoperative CA19-9 and histology grade on the prognosis of patients with PDAC. Methods: A total of 612 patients with PDAC undergoing curative pancreatectomy were retrospectively enrolled. A biological risk model was established based on preoperative CA19-9 and histology grade. Prognostic significance of the biological risk was evaluated. Results: 360 (58.8%) patients had preoperative CA19-9>112 U/ml and 348 (56.9%) patients had high histology grade. Biological risk based on preoperative CA19-9 and histology grade was independently associated with survival of PDAC patients. The biological risk was incorporated into the eighth edition of the TNM staging system and a modified TNM (mTNM) staging system was developed. The ROC curves showed that the area under curve(AUC) of the mTNM staging system was significantly greater than that of the TNM staging system. Conclusion: Biological risk based on preoperative CA19-9 and histology grade was an independent prognostic factors for patients with PDAC. Incorporating the biological risk into the TNM staging system could improve the the accuracy of the TNM staging system in predicting prognosis of PDAC.